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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00426764




Registration number
NCT00426764
Ethics application status
Date submitted
23/01/2007
Date registered
25/01/2007
Date last updated
11/02/2020

Titles & IDs
Public title
A Trial of Romidepsin for Progressive or Relapsed Peripheral T-cell Lymphoma
Scientific title
A Phase II, Multicenter, Open-Label Trial Evaluating The Activity And Tolerability Of Romidepsin (Depsipeptide, FK228) In Progressive Or Relapsed Peripheral T-Cell Lymphoma Following Prior Systemic Therapy (GPI-06-0002)
Secondary ID [1] 0 0
2006-006228-21
Secondary ID [2] 0 0
GPI-06-0002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Peripheral T-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Romidepsin

Experimental: Romidepsin - Participants received romidepsin 14 mg/m\^2 administered intravenously over 4 hours on Days 1, 8, and 15 of a 28-day cycle. Participants continued on monthly cycles of romidepsin. The planned duration of study therapy was 6 cycles. Patients who responded could continue beyond 6 cycles until disease progression or other withdrawal criteria were met. For participants treated for 12 or more cycles, maintenance dosing (2 doses per cycle) was permitted.


Treatment: Drugs: Romidepsin
Romidepsin intravenously (through a vein) over 4 hours on Days 1, 8 and 15 of each 28-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With a Complete Response According to the International Workshop Response Criteria (IWC) for Non-Hodgkin's Lymphomas (NHL) Assessed by an Independent Review Committee
Timepoint [1] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [1] 0 0
Percentage of Participants With Objective Disease Response
Timepoint [1] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [2] 0 0
Duration of Objective Disease Response
Timepoint [2] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [3] 0 0
Duration of Complete Disease Response
Timepoint [3] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [4] 0 0
Time to Disease Progression
Timepoint [4] 0 0
Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [5] 0 0
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [5] 0 0
From Baseline up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary outcome [6] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [6] 0 0
From first dose of study treatment until the final study visit, which occurred 30 days after receiving the last dose. Mean duration of treatment up until 30 September 2012 (data cutoff for analysis) was 169 days.

Eligibility
Key inclusion criteria
Patients must fulfill all of the following criteria to be eligible for study participation and have:

* Histologically confirmed PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous ?d T-cell lymphoma (excludes mycosis fungoides or Sezary syndrome), transformed mycosis fungoides, hepatosplenic T-cell lymphoma, anaplastic large cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK]-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after autologous stem cell transplant (ASCT);
* Age =18 years;
* Written informed consent;
* Progressive disease following at least one systemic therapy or refractory to at least one prior systemic therapy;
* Measurable disease according to the International Workshop Response (IWC) criteria and/or measurable cutaneous disease;
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
* Serum potassium =3.8 mmol/L and magnesium =0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);
* Negative urine or serum pregnancy test on females of childbearing potential; and
* All women of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device [IUCD] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male patients should use a barrier method of contraception during the treatment period and for at least 1 month thereafter. Hormonal methods of contraception such as the contraceptive pill or patch (particularly those containing ethinyl-estradiol) should be avoided due to a potential drug interaction.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients are ineligible for entry if any of the following criteria are met:

* Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic resonance imaging (MRI) scans are required only if brain metastasis is suspected clinically];
* Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas given);
* Initiation of corticosteroids during study (defined as 7 days prior to Cycle 1 Day 1[C1D1] until study drug discontinuation)

* Patients treated with a pulse of steroids were to discontinue steroid use 7 days prior to C1D1 and have a repeat CT scan and disease assessment after discontinuation of corticosteroids and before starting romidepsin;
* Concomitant use of any other anti-cancer therapy;
* Concomitant use of any investigational agent;
* Use of any investigational agent within 4 weeks of study entry;
* Any known cardiac abnormalities such as:

* Congenital long QT syndrome;
* QTc interval >480 milliseconds (msec);
* A myocardial infarction within 6 months of C1D1. Patients with a history of myocardial infraction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;
* Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
* Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should be referred to a cardiologist for evaluation;
* An ECG recorded at screening showing significant ST depression (ST depression of =2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the end of the QRS complex). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
* Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI;
* A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
* Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above);
* Uncontrolled hypertension, i.e., blood pressure (BP) of =160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria;
* Any cardiac arrhythmia requiring anti-arrhythmic medication;
* Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);
* Concomitant use of drugs that may cause a significant prolongation of the QTc;
* Concomitant use of CYP3A4 significant or moderate inhibitors;
* Concomitant use of therapeutic warfarin or another anticoagulant due to a potential drug interaction. Use of a small dose of a anticoagulant to maintain patency of venous access port and cannulas is permitted;
* Clinically significant active infection;
* Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C;
* Previous extensive radiotherapy involving =30% of bone marrow (e.g., whole pelvis, half spine), excluding patients who have had total body irradiation as part of a conditioning regimen for ASCT;
* Major surgery within 2 weeks of study entry;
* Previous allogeneic stem cell transplant;
* Inadequate bone marrow or other organ function as evidenced by:

* Hemoglobin <9 g/dL (transfusions and/or erythropoietin are permitted);
* Absolute neutrophil count (ANC) =1.0 × 10^9 cells/L [patients with neutropenia (ANC 1-1.5 10^9 cells/L) as a function of their disease may be supported with granulocyte-colony stimulating factor (G-CSF)];
* Platelet count <100 × 10^9 cells/L or platelet count <75 × 10^9 cells/L if bone marrow disease involvement is documented;
* Total bilirubin >2.0 × upper limit of normal (ULN) or >3.0 × ULN in the presence of demonstrable liver metastases;
* Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 × ULN or >3.0 × ULN in the presence of demonstrable liver metastases; or
* Serum creatinine >2.0 × ULN;
* Patients who are pregnant or breast-feeding;
* Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix (CIN 1) that has been treated curatively);
* Any prior history of a hematologic malignancy (other than T-cell lymphoma);
* Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures; or
* Prior exposure to romidepsin (other histone deacetylase inhibitors are allowed).

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/06/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/05/2018
Sample size
Target
Accrual to date
Final
131
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Mater Private Medical Centre - Haematology and Oncology Clinics of Australasia Research Centre - South Brisbane
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [3] 0 0
St. Vincent Hospital - Fitzroy
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Hradec Kralove
Country [24] 0 0
Czechia
State/province [24] 0 0
Prague 10
Country [25] 0 0
Czechia
State/province [25] 0 0
Prague 2
Country [26] 0 0
France
State/province [26] 0 0
Bordeaux
Country [27] 0 0
France
State/province [27] 0 0
Créteil
Country [28] 0 0
France
State/province [28] 0 0
Lille
Country [29] 0 0
France
State/province [29] 0 0
Nantes
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Pessac
Country [32] 0 0
France
State/province [32] 0 0
Pierre Bénite
Country [33] 0 0
France
State/province [33] 0 0
Rennes
Country [34] 0 0
France
State/province [34] 0 0
Rouen Cedex
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Frankfurt a.M.
Country [37] 0 0
Germany
State/province [37] 0 0
Göttingen
Country [38] 0 0
Germany
State/province [38] 0 0
Köln
Country [39] 0 0
Germany
State/province [39] 0 0
Muenchen
Country [40] 0 0
Germany
State/province [40] 0 0
Nürnberg
Country [41] 0 0
Germany
State/province [41] 0 0
Tuebingen
Country [42] 0 0
Poland
State/province [42] 0 0
Gdansk
Country [43] 0 0
Poland
State/province [43] 0 0
Kraków
Country [44] 0 0
Poland
State/province [44] 0 0
Lodz
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Pamplona
Country [49] 0 0
Spain
State/province [49] 0 0
Salamanca
Country [50] 0 0
Spain
State/province [50] 0 0
Santandar
Country [51] 0 0
Sweden
State/province [51] 0 0
Lund
Country [52] 0 0
Sweden
State/province [52] 0 0
Uppsala
Country [53] 0 0
Ukraine
State/province [53] 0 0
Dnipropetrovsk
Country [54] 0 0
Ukraine
State/province [54] 0 0
Kyiv
Country [55] 0 0
Ukraine
State/province [55] 0 0
Lviv
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London Hampstead
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the activity of romidepsin in patients with progressive or relapsed peripheral T-cell lymphoma (PTCL) who have already been treated with systemic therapy.
Trial website
https://clinicaltrials.gov/study/NCT00426764
Trial related presentations / publications
Foss F, Pro B, Miles Prince H, Sokol L, Caballero D, Horwitz S, Coiffier B. Responses to romidepsin by line of therapy in patients with relapsed or refractory peripheral T-cell lymphoma. Cancer Med. 2017 Jan;6(1):36-44. doi: 10.1002/cam4.939. Epub 2016 Dec 16.
Shustov A, Coiffier B, Horwitz S, Sokol L, Pro B, Wolfson J, Balser B, Eisch R, Popplewell L, Prince HM, Allen SL, Piekarz R, Bates S. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma. 2017 Oct;58(10):2335-2341. doi: 10.1080/10428194.2017.1295143. Epub 2017 Mar 7.
Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Borchmann P, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan S, Shustov A, Nichols J, Carroll S, Balser J, Balser B, Horwitz S. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012 Feb 20;30(6):631-6. doi: 10.1200/JCO.2011.37.4223. Epub 2012 Jan 23.
Horwitz S, Coiffier B, Foss F, Prince HM, Sokol L, Greenwood M, Caballero D, Morschhauser F, Pinter-Brown L, Iyer SP, Shustov A, Nichols J, Balser J, Balser B, Pro B. Utility of (1)(8)fluoro-deoxyglucose positron emission tomography for prognosis and response assessments in a phase 2 study of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015 Apr;26(4):774-779. doi: 10.1093/annonc/mdv010. Epub 2015 Jan 20.
Foss F, Horwitz S, Pro B, Prince HM, Sokol L, Balser B, Wolfson J, Coiffier B. Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial. J Hematol Oncol. 2016 Mar 10;9:22. doi: 10.1186/s13045-016-0243-8. Erratum In: J Hematol Oncol. 2017 Sep 18;10(1):154. doi: 10.1186/s13045-017-0518-8.
Foss F, Coiffier B, Horwitz S, Pro B, Prince HM, Sokol L, Greenwood M, Lerner A, Caballero D, Baran E, Kim E, Nichols J, Balser B, Wolfson J, Whittaker S. Tolerability to romidepsin in patients with relapsed/refractory T-cell lymphoma. Biomark Res. 2014 Sep 8;2:16. doi: 10.1186/2050-7771-2-16. eCollection 2014.
Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan Iyer S, Shustov A, Nielsen T, Nichols J, Wolfson J, Balser B, Horwitz S. Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses. J Hematol Oncol. 2014 Jan 23;7:11. doi: 10.1186/1756-8722-7-11.
Public notes

Contacts
Principal investigator
Name 0 0
Myron Czuczman, MD
Address 0 0
Celgene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00426764